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United States Patent |
5,324,870
|
Sano
,   et al.
|
June 28, 1994
|
Process for producing optically active 1-substituted-1,3-propanediols
using ruthenium-phosphine complex as a catalyst
Abstract
A process for producing an optically active 1-substituted-1,3-propanediol
is disclosed, comprising hydrogenating a 3-substituted-3-oxopropanol or
3-substituted-3-oxopropanal in the presence of a ruthenium-phosphine
complex represented by formula (I):
[RuI(p-cymene)(R.sup.1 BINAP)]I.sub.3 (I)
wherein R.sup.1 -BINAP represents an optically active tertiary phosphine
represented by formula (II):
##STR1##
wherein R.sup.1 represents a phenyl group which may be substituted with a
lower alkyl group or a halogen atom at the p-position and/or m-position.
Inventors:
|
Sano; Noboru (Kanagawa, JP);
Sayo; Noboru (Kanagawa, JP);
Kumobayashi; Hidenori (Kanagawa, JP)
|
Assignee:
|
Takasago International Corporation (Tokyo, JP)
|
Appl. No.:
|
155830 |
Filed:
|
November 23, 1993 |
Foreign Application Priority Data
Current U.S. Class: |
568/863; 556/21; 568/862 |
Intern'l Class: |
C07C 029/14; C07C 027/04 |
Field of Search: |
568/862,863
556/21
|
References Cited
U.S. Patent Documents
4503274 | Mar., 1985 | Arena | 568/863.
|
4608446 | Aug., 1986 | Mohring et al. | 568/863.
|
4739084 | Apr., 1988 | Takaya et al. | 556/21.
|
4739085 | Apr., 1988 | Takaya et al. | 556/21.
|
4777302 | Oct., 1988 | Haji et al. | 568/862.
|
4960960 | Oct., 1990 | Harrison et al. | 568/881.
|
4994590 | Feb., 1991 | Takaya et al. | 556/21.
|
Foreign Patent Documents |
55-61937 | Oct., 1980 | JP.
| |
Other References
J. Chem. Soc., Chem. Commun., 1985, 922-924.
J. Org. Chem., 1988, 53, 4081-4084.
|
Primary Examiner: Lone; Werren B.
Attorney, Agent or Firm: Sughrue, Mion, Zinn, Macpeak & Seas
Parent Case Text
This is a continuation-in-part of application Ser. No. 07/964,904, filed
Oct. 22, 1992, now U.S. Pat. No. 5,286,888.
Claims
What is claimed is:
1. A process for producing an optically active
1-substituted-1,3-propanediol represented by formula (III):
##STR9##
wherein R.sup.2 represents a lower alkyl group, a benzyl group or a phenyl
group which may have a substituent group, and * designates an asymmetric
carbon atom, which comprises hydrogenating a 3-substituted-3-oxopropanol
or 3-substituted-3-oxopropanal represented by formula (IV):
##STR10##
wherein R.sup.2 is as defined above, and R.sup.3 represents --CHO or
--CH.sub.2 OH in the presence of a ruthenium-phosphine complex represented
by formula (I):
[RuI(p-cymene) (R.sup.1 -BINAP)]I.sub.3 (I)
wherein R.sup.1 -BINAP represents an optically active tertiary phosphine
represented by formula (II):
##STR11##
wherein R.sup.1 represents a phenyl group which may be substituted with a
lower alkyl group or a halogen atom at the p-position and/or m-position.
Description
FIELD OF THE INVENTION
The present invention relates to a ruthenium-phosphine complex useful as a
catalyst for various organic synthetic reactions, particularly
enantioselective hydrogenation reactions and to a process for producing
optically active 1-substituted-1,3-propanediols using the same.
BACKGROUND OF THE INVENTION
A large number of organic synthetic reactions using a transition metal
complex as a catalyst have hitherto been developed and made use of for
various purposes. In particular, many reports have been made on
enantioselective catalysts used for enantioselective synthetic reactions,
such as enantioselective hydrogenation and enantioselective isomerization.
Among them, metal complexes in which an optically active tertiary
phosphine compound is coordinated to metallic rhodium or ruthenium are
well known as catalysts for enantioselective hydrogenation reactions.
For example, a rhodium-phosphine complex using
2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (hereinafter abbreviated as
BINAP) as a ligand is disclosed in JP-A55-61937 (the term "JP-A" as used
herein means an "unexamined published Japanese patent application").
With regard to ruthenium, ruthenium complexes obtained by using BINAP or
2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl (hereinafter abbreviated as
Tol-BINAP) as a ligand, such as Ru.sub.2 Cl.sub.4 (BINAP).sub.2 NEt.sub.3
(wherein Et represents an ethyl group) and Ru.sub.2 Cl.sub.4
(Tol-BINAP).sub.2 NEt.sub.3 have been reported (Ikariya et al., J. Chem.
Soc., Chem. Commun., p. 922 (1985)). Also, Ru(O.sub.2 CR.sup.4).sub.2
(BINAP) and Ru(O.sub.2 CR.sup.4).sub.2 (Tol-BINAP) (wherein R.sup.4
represents a lower alkyl group or a lower alkyl-substituted phenyl group)
have been disclosed in JP-A-62-265293; and [RuH.sub.l (R.sup.5
-BINAP).sub.m ]Z.sub.n (wherein R.sup.5 represents a hydrogen atom or a
methyl group; Z represents ClO.sub.4, BF.sub.4, or PF.sub.6 ; when l is 0,
then m represents 1, and n represents 2; and when l is 1, then m
represents 2, and n represents 1) has been disclosed in JP-A-63-41487.
However, these ruthenium complexes were complicated in their preparation
and had such disadvantages as low yield and poor stability.
Furthermore, JP-A-2-191289 has reported [RuX.sub.l (S).sub.m (R.sup.6
-BINAP)]Y.sub.n (wherein R.sup.6 represents a hydrogen atom or a methyl
group; X represents a halogen atom; S represents benzene which may be
substituted or acetonitrile; Y represents a halogen atom, ClO.sub.4,
PF.sub.6, BPh.sub.4 (wherein Ph represents a phenyl group), or BF.sub.4 ;
in the case where S is benzene which may be substituted, l is 1, m is 1,
and n is 1; and in the case where S is acetonitrile, when l is 1, then m
is 2, and n is 1, and when l is 0, then m is 4, and n is 2). However, even
when these phosphine complexes are used, there were sometimes problems in
their practical applications on an industrial scale, such as insufficiency
in catalytic activity, duration, and enantioselectivity depending on the
reactions and reaction substrates.
On the other hand, optically active 1-substituted-1,3-propanediols are
useful intermediates in enantioselective synthesis for the production of
pharmaceuticals, liquid crystal compounds, and natural products. Among
these, as a production method of optically active 1-phenyl-1,3-propanediol
which is useful as an intermediate of pharmaceuticals such as fluoxetine
and tomoxetine, a method in which cinnamyl alcohol is subjected to
enantioselective epoxidation to obtain optically active epoxycinnamyl
alcohol, which is then reduced by Red-Al (sodium
bis(2-methoxyethoxy)aluminum hydride) is reported (Y. Gao, et al., J. Org.
Chem., 53, pp. 4081-4084 (1988)). In the above method, however, not only
Red-Al which is difficult to handle is employed, but products having a
satisfactorily high optical purity cannot be obtained.
SUMMARY OF THE INVENTION
Accordingly, an object of the present invention is to provide a catalyst
having high catalytic activity and long duration and capable of giving
high enantioselectivity in enantioselective reactions, that is, producing
products having a high optical purity. In addition, another object of the
present invention is to provide a useful production process of optically
active 1-substituted-1,3-propanediols which are important as an
intermediate for synthesis of, for example, pharmaceuticals.
Under these circumstances, the present inventors have conducted extensive
studies on catalysts having higher activities. As a result, it has been
found that certain ruthenium-phosphine complexes having four iodine atoms
coordinated therewith have much higher catalytic activities and longer
duration than complexes having a lower number of iodine atoms coordinated
therewith and that complexes having optically inactive ligands can be used
as catalysts for ordinary syntheses, whereas those having optically active
ligands can be used as catalysts they are used for enantioselective
hydrogenation reactions of 3-oxopropanols or 3-oxopropanals,
1-substituted-1,3-propanediols having a high optical purity can be
obtained in high yield. The present invention has been completed based on
these findings.
The present invention relates to a ruthenium-phosphine complex represented
by formula (I):
[RuI(p-cymene)(R.sup.1 -BINAP)]I.sub.3 (I)
wherein R.sup.1 -BINAP represents a tertiary phosphine represented by
formula (II):
##STR2##
wherein R.sup.1 represents a phenyl group which may be substituted with a
lower alkyl group or a halogen atom at the p-position and/or m-position.
The present invention also relates to a process for producing an optically
active 1-substituted-1,3-propanediol represented by formula (III):
##STR3##
wherein R.sup.2 represents a lower alkyl group, a benzyl group or a phenyl
group which may have a substituent group, and * designates an asymmetric
carbon atom, which comprises hydrogenating a 3-substituted-3-oxopropanol
or 3-substituted-3-oxopropanal represented by formula (IV):
##STR4##
wherein R.sup.2 is as defined above, and R.sup.3 represents --CHO or
--CH.sub.2 OH, in the presence of a ruthenium-phosphine complex
represented by formula (I) having an optically active tertiary phosphine
coordinated therewith as a ligand.
DETAILED DESCRIPTION OF THE INVENTION
In the ruthenium-phosphine complex represented by formula (I) of the
present invention, R.sup.1 represents a phenyl group which may be
substituted with a lower alkyl group or a halogen atom at the p-position
and/or m-position, and specific examples thereof include a phenyl group, a
p-tolyl group, an m-tolyl group, a p-tert-butylphenyl group, a
3,5-dimethylphenyl group, a p-chlorophenyl group, and 3,5-dichlorophenyl
group.
The ruthenium-phosphine complex (I) of the present invention can be
prepared, for example, according to the following reaction scheme in which
a ruthenium-phosphine complex of formula (V) as described in JP-A-2-191289
is reacted with iodine:
##STR5##
wherein R.sup.1 -BINAP is as defined above.
This reaction is carried out with stirring in a suitable solvent such as
methanol at 15.degree. to 30.degree. C. for 1 to 5 hours.
Though the ruthenium-phosphine complex (I) of the present invention can be
isolated and then used, it can be used as a catalyst for enantioselective
synthesis, etc. while mixing the starting complex (V) and iodine to
generate it in the reaction mixture. In this case, the amount of iodine
added is from 1 to 10 mole, and preferably from 2 to 4 mole per mole of
the starting complex (V).
The thus obtained ruthenium-phosphine complex (I) of the present invention
can be used as a catalyst of various organic synthetic reactions. When a
complex comprising an optically active tertiary phosphine as R.sup.1
-BINAP is used, it is particularly useful as a catalyst of
enantioselective synthetic reactions such as enantioselective
hydrogenation. In the case of enantioselective hydrogenation, for example,
the complex (I) of the present invention exhibits about 10 times the
catalytic activity of the complex (V) as disclosed in JP-A-2-191289.
Next, the process for producing a 1-substituted-1,3-propanediol by using
the complex (I) of the present invention as an enantioselective
hydrogenation catalyst is explained. This producing process is illustrated
by the following reaction scheme:
##STR6##
wherein R.sup.2 and R.sup.3 are as defined above.
In the above reaction scheme, R.sup.2 of the compound (IV) represents a
lower alkyl group, a benzyl group or a phenyl group which may have a
substituent group. Specific examples of the lower alkyl group include a
methyl group, an ethyl group, a propyl group, a butyl group, an isopropyl
group, and a tert-butyl group; and specific examples of the phenyl group
which may have a substituent group include a phenyl group, an m-tolyl
group, a p-tolyl group, a p-chlorophenyl group, a p-methoxyphenyl group,
and a 3,4,5-trimethoxyphenyl group.
As the starting compound (IV) of the present reaction,
3-substituted-3-oxopropanols and 3-substituted-3-oxopropanals can be used.
These compounds can be synthesized, for example, as follows.
##STR7##
In the above reaction scheme, R.sup.2 is as defined above; R.sup.7 and
R.sup.8, which may be the same or different, each represents a lower alkyl
group; and M represents lithium, sodium, or potassium.
That is, the ketone (VI) is condensed with the lower formic acid ester
(VII) by using the metallic alkoxide (VIII) to obtain the compound (IX),
which is then neutralized with a mineral acid to produce the aldehyde
(IVa).
##STR8##
In the above reaction scheme, R.sup.2 is as defined above.
That is, the alcohol (IVb) can be synthesized by condensing the ketone (VI)
and formaldehyde with a mineral acid as a catalyst.
With respect to the ruthenium-phosphine complex (I) to be used in an
enantioselective hydrogenation reaction of the present invention, a
complex having an optically active ligand R.sup.1 -BINAP, i.e., the (R)-
or (S)-compound, can be used. In this case, final products having a
desired absolute configuration can be obtained depending on the selection.
Such a ruthenium-phosphine complex (I) can be used in an amount of
1/10,000 to 1/10 mole, and preferably 1/2,000 to 1/200 mole per mole of
the substrate compound (IV).
In carrying out the present reaction, for example, the compound (IV) and
the ruthenium-phosphine complex (I) are added to an appropriate solvent in
a nitrogen atmosphere to obtain a homogeneous solution, which is then
reacted for 5 to 150 hours, and preferably 7 to 50 hours under a hydrogen
pressure of 10 to 150 atm, and preferably 20 to 100 atm at a reaction
temperature of 10.degree. to 100.degree. C., and preferably 25.degree. to
60.degree. C.
Examples of the solvents used include alcohols such as methanol, ethanol,
and isopropanol; halogenated compounds such as methylene chloride,
1,2-dichloroethane, and trichloroethylene; and ethers such as diethyl
ether and diisopropyl ether. These solvents can be used singly or in
combination.
Purification of the reaction product can be carried out by known methods
including silica gel column chromatography and recrystallization (using a
solvent such as diethyl ether, diisopropyl ether, benzene, and toluene).
The optically active 1-substituted-1,3-propanediol compound (III) thus
obtained is a useful intermediate of, for example, pharmaceuticals. For
example, optically active 1-phenyl-1,3-propanediol is an important
synthetic intermediate of fluoxetine and tomoxetine useful as an
antidepressant.
As explained above, the ruthenium-phosphine complex of the present
invention is industrially useful as a catalyst excellent in
enantioselectivity, and particularly in catalytic activity, which can be
employed in organic synthetic reactions such as enantioselective synthetic
reactions. In particular, when used as a catalyst for enantioselective
hydrogenation of a 3-substituted-3-oxopropanol or a
3-substituted-3-oxopropanal, it produces a 1-substituted-1,3-propanediol
useful as an intermediate of pharmaceuticals in high yield.
The present invention is now illustrated in greater detail with reference
to Examples and Comparative Examples, but it should not be understood that
the present invention is construed as being limited thereto. Each
measurement of the present invention was undertaken on the following
instruments and under the following conditions, unless otherwise noted.
.sup.1 H-NMR and .sup.31 P-NMR: Model AM-400 (400 MHz) (manufactured by
Bruker, Inc.)
Internal Standard: .sup.1 H-NMR . . . tetramethylsilane
External Standard: .sup.31 NMR . . . 85% phosphoric acid
Optical Rotation: Model DIP-4 (manufactured by JASCO Inc.)
Optical Purity (High-performance Liquid Chromatography):
Liquid Chromatograph: Hitachi L-6000 (manufactured by Hitachi Ltd.)
Column: CHIRALCEL OB (.phi.4.6 mm.times.250 mm) (manufactured by Daicel
Chemical Industries, Ltd.)
Eluent: Hexane/Isopropanol (93/7 by volume)
Flow Rate: 1 ml/min.
Detector: UV Detector L-4000 (manufactured by Hitachi Ltd.) (UV-254 nm)
The abbreviations used in Examples and Comparative Examples are as follows.
BINAP: 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl
Tol-BINAP: 2,2'-Bis(di-p-tolylphosphino)-1,1'-binaphthyl
DM-BINAP: 2,2'-Bis[di(3,5-dimethylphenyl)phosphino]-1,1'-binaphthyl
p-Cl-BINAP: 2,2'-Bis[di(p-chlorophenyl)phosphino]-1,1'-binaphthyl
EXAMPLE 1
Synthesis of [RuI(p-cymene)((R)-BINAP)]I.sub.3
In a 500 ml flask with side arm was charged 5.0 g (4.5 mmole) of
[RuI(p-cymene)((R)-BINAP)]I in a nitrogen atmosphere, and 270 ml of
methanol was added thereto, followed by stirring the mixture at room
temperature for 30 minutes. Then, 30 ml of a methanol solution of 3.5 g
(13.5 mmole) of iodine was added thereto, and the mixture was stirred at
room temperature for 90 minutes. The precipitated crystal was collected by
filtration and dried for 24 hours at room temperature under reduced
pressure (1 mmHg) to give 5.9 g (percent yield: 96%) of the titled
compound.
.sup.31 P-NMR (400 MHz, CDCl.sub.3) .delta. ppm: 24.95 (d, J=59.8 Hz),
41.05 (d, J=59.6 Hz)
Elemental analysis for C.sub.54 H.sub.46 P.sub.2 RuI.sub.4 :
Calcd. (%): C 47.50; H 3.40
Found (%): C 47.61; H 3.12
Solubility: 1 g/5,700 ml (methanol, 25.degree. C.)
(The solubility of [RuI(p-cymene)((R)-BINAP)]I was 1 g/370 ml of methanol
at 25.degree. C.)
EXAMPLE 2
Synthesis of [RuI(p-cymene]((R)-Tol-BINAP)]I.sub.3
The titled complex was obtained (percent yield: 97.5%) in the same manner
as in Example 1, except for replacing (R)-BINAP with (R)-Tol-BINAP as a
ligand.
.sup.31 P-NMR (400 MHz, CDCl.sub.3) .delta. ppm: 23.36 (d, J=59.7 Hz),
39.31 (d, J=58.9 Hz)
Elemental analysis for C.sub.58 H.sub.54 P.sub.2 RuI.sub.4 :
Calcd. (%): C 49.00; H 3.83
Found (%): C 48.72; H 3.63
Solubility: 1 g/1,400 ml (methanol, 25.degree. C.)
(The solubility of [RuI(p-cymene)((R)-TolBINAP)]I was 1 g/95 ml of methanol
at 25.degree. C.)
EXAMPLE 3
Synthesis of [RuI(p-cymene)((R)-DM-BINAP)]I.sub.3
The titled complex was obtained (percent yield: 94.3%) in the same manner
as in Example 1, except for replacing (R)-BINAP with (R)-DM-BINAP as a
ligand.
.sup.31 P-NMR (400 MHz, CDCl.sub.13) .delta. ppm: 25.70 (d, J=58.7 Hz),
39.32 (d, J=58.9 Hz)
Elemental analysis for C.sub.62 H.sub.62 P.sub.2 RuI.sub.4 :
Calcd. (%): C 50.39; H 4.23
Found (%): C 50.27; H 4.20
EXAMPLE 4
Synthesis of [RuI(p-cymene)((R)-p-Cl-BINAP)]I.sub.3
The titled complex was obtained (percent yield: 2.1%) in the same manner as
in Example 1, except for replacing (R)-BINAP with (R)-p-Cl-BINAP as a
ligand.
.sup.31 P-NMR (400 MHz, CDC13) .delta. ppm: 24.65 (d, J=59.7 Hz), 39.88 (d,
J=59.8 Hz)
Elemental analysis for Chd54H.sub.42 Cl.sub.4 P.sub.2 RuI.sub.4
Calcd. (%): C 43.14; H 2.82
Found (%): C 43.02; H 2.61
EXAMPLE 5
Enantioselective Hydrogenation of 3-Phenyl-3-oxopropanol
In a 500 ml stainless steel-made autoclave were charged 65 g (400 mmole) of
3-phenyl-3-oxopropanol and 550 mg (0.4 mmole) of
[RuI(p-cymene)((R)-BINAP)]I.sub.3 synthesized in Example 1 in a nitrogen
atmosphere, and 300 ml of methanol was added thereto, followed by stirring
the mixture at 30.degree. C. for 20 hours under a hydrogen pressure of 30
atm. The reaction mixture was concentrated and subjected to silica gel
column chromatography (eluent: hexane/isopropanol=9/l by volume) to
eliminate the complex. The obtained hydrogenation product was dissolved in
a 6-fold amount of diisopropyl ether by heating and allowed to stand at
0.degree. C. for 24 hours. The resulting precipitate was collected by
filtration and dried (room temperature, 1 mmHg), and 45.5 g of
(1S)-phenyl-1,3-propanediol was obtained as a colorless crystal (percent
yield: 70.0%).
m.p.: 64.9.degree. C.
[a].sub.D.sup.25 : -41.2.degree. C. (c=1.0, methanol)
.sup.1 H-NMR (400 MHz, CDCl.sub.3) .delta. ppm: 1.88-2.03 (m, 2H),
2.88-3.02 (br s, 1H) 3.79-3.88 (m, 2H), 4.89-4.94 (m, 1H) 7.25-7.38 (m,
5H)
The obtained (1S)-phenyl-1,3-propanediol was subjected to high-performance
liquid chromatography. As a result, it was found to have an optical purity
of 99.9% ee.
REFERENCE EXAMPLE 1
Synthesis of Sodium Salt of 3-Phenyl-3-oxopropanal
In a 1,000 ml four-necked flask were charged 360 ml of dried toluene and
212 g (1.1 mole) of a 28% methanol solution of sodium methylate. The
mixture was heated at 50.degree. C., and 120 g (1.0 mole) of acetophenone
and 111 g (1.5 mole) of ethyl formate were added thereto, followed by
stirring the mixture at 50.degree. C. for 20 hours. The resulting
precipitate was collected by filtration and dried at 50.degree. C. under
reduced pressure (1 mmHg) for 6 hours to obtain 145 g of the desired
sodium salt as a pale yellow crystal (percent yield: 85.3%).
.sup.1 H-NMR (400 MHz, D.sub.2 O) .delta. ppm: 7.40-7.72 (m, 6H), 9.02 (br
s, 1H)
REFERENCE EXAMPLE 2
Synthesis of 3-Phenyl-3-oxopropanal
In a 200 ml four-necked flask were charged 25 ml of diisopropyl ether and
62.5 ml of 20% aqueous hydrochloric acid in a nitrogen atmosphere,
followed by vigorously stirring the mixture at room temperature.
Subsequently, 62.5 ml of an aqueous solution of 25.53 g (1.5 mmole) of the
sodium salt prepared in Reference Example 1 was slowly added thereto,
followed by vigorously stirring the mixture at room temperature for 1
hour. The reaction mixture was subjected to liquid separation in a
nitrogen atmosphere, and the organic layer was washed with 25 ml of
purified water. The desired 3-phenyl-3-oxopropanal was obtained as a
diisopropyl ether solution. The titled compound was used in the subsequent
reaction without being isolated and purified.
.sup.1 H-NMR (400 MHz, CDCl.sub.3) .delta. ppm: 7.30-8.40 (m, 8H)
EXAMPLE 6
Enantioselective Hydrogenation of 3-Phenyl-3-oxopropanal
In a 200 ml stainless steel-made autoclave were charged 426.5 mg of
[RuI(p-cymene)(R)-Tol-BINAP]I.sub.3 prepared in Example 2, the diisopropyl
ether solution of 3-phenyl-3-oxopropanal prepared in Reference Example 2,
100 ml of methanol, and 2.0 ml of degassed purified water in a nitrogen
atmosphere, followed by stirring the mixture at 50.degree. C. for 22 hours
under a hydrogen pressure of 50 atm. The reaction mixture was concentrated
and subjected to silica gel column chromatography (eluent:
hexane/isopropanol=9/l by volume) to eliminate the complex. The obtained
hydrogenation product was dissolved in a 6-fold amount of diisopropyl
ether by heating and allowed to stand at 0.degree. C. for 24 hours. The
resulting precipitate was collected by filtration and dried (room
temperature, 1 mmHg), and 10.5 g of (1S)-phenyl-1,3-propanediol was
obtained as a colorless crystal (percent yield: 45%).
EXAMPLES 7 TO 10 AND COMPARATIVE EXAMPLES 1 TO 2
Enantioselective Hydrogenation of 3-Phenyl-3-oxopropanol
(S)-1-Phenyl-1,3-propanediol was obtained in the same manner as in Example
5, except for changing the kind and amount of ruthenium-optically active
phosphine complex, the hydrogen pressure, and the reaction time and for
adding iodine, if desired. The reaction conditions and the results
obtained are given in Table 1.
TABLE 1
__________________________________________________________________________
Hydrogen
Reaction Chemical
Optical
Ruthenium-Optically Pressure
Time Conversion
Purity
Purity
Example No.
Active Phosphine Complex
s/c.sup.(1)
Additive.sup.(2)
(atm) (hr) (%) (%) (%
__________________________________________________________________________
ee)
7 [RuI(p-cymene)(R)-BINAP)]I.sub.3
500 100 20 97.6 97.2 87.6
8 [RuI(p-cymene)(R)-BINAP)]I.sub.3
1000 100 20 89.2 97.2 86.4
9 [RuI(p-cymene)(R)-BINAP)]I
500 Iodine (3)
100 20 99.1 91.9 78.8
10 [RuI(p-cymene)(R)-BINAP)]I
1000
Iodine (3)
100 20 94.4 98.9 91.0
Comparative
[RuI(p-cymene)(R)-BINAP)]I
100 100 22.5 99.7 97.6 82.2
Example 1
Comparative
[RuI(p-cymene)(R)-BINAP)]I
500 100 20.5 45.5 96.4 87.4
Example 2
__________________________________________________________________________
.sup.(1) The value of s/c represents a molar ratio of the substrate to th
rutheniumoptically active phosphine complex.
.sup.(2) The number in the parenthesis represents a molar equivalent of
the additive to the rutheniumoptically active phosphine complex.
EXAMPLE 11
Synthesis of 3-Methyl-3-hydroxypropanol
In a 500 ml stainless steel-made autoclave were charged 35.2 g (400 mmole)
of 3-methyl-3-oxopropanol and 550 mg (0.4 mmole) of
[RuI(p-cymene)((R)-BINAP)]I.sub.3 synthesized in Example 1 in a nitrogen
atmosphere, and 300 ml of methanol was added thereto, followed by stirring
the mixture at 35.degree. C. for 19 hours under a hydrogen pressure of 50
atm. The reaction mixture was concentrated by using rotary evaporator and
subjected to distillation by using Claisen flask to obtain
3-methyl-3-hydroxypropanol (b.p.: 78.degree. C., fraction under 0.1 mmHg:
33.8 g (96%)). The thus obtained product was derived to the
.alpha.-methoxy-.alpha.-(trifluoromethyl)phenylacetic acid (MTPA) diester
and subjected to high-performance liquid chromatography (column:
Cosmosil-5 SL, eluent: hexane/ether 9/l by volume). As a result, it was
found to have an optical purity of 98% ee.
EXAMPLE 12
Synthesis of 3-Benzyl-3-hydroxypropanol
In a 500 ml stainless steel-made autoclave were charged 65.6 g (400 mmole)
of 3-benzyl-3-oxopropanol and 550 mg (0.4 mmole) of
[RuI(p-cymene)((R)-BINAP)]I.sub.3 synthesized in Example 1 in a nitrogen
atmosphere, and 300 ml of methanol was added thereto, followed by stirring
the mixture at 35.degree. C. for 20 hours under a hydrogen pressure of 50
atm. The reaction mixture was concentrated by using rotary evaporator and
then subjected to silica gel column chromatography (eluent:
hexane/ethylacetate=8/2 by volume) to eliminate the complex to give 63 g
of 3-benzyl-3-hydroxypropanol (96% yield). The thus obtained product was
derived to the MTPA diester and subjected to high-performance liquid
chromatography (column: Cosmosil-5SL, eluent: hexane/ether=8/2 by volume).
As a result, it was found to have an optical purity of 97% ee.
While the invention has been described in detail and with reference to
specific embodiments thereof, it will be apparent to one skilled in the
art that various changes and modifications can be made therein without
departing from the spirit and scope thereof.
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